Pichkur Evgeny B, Vorovitch Mikhail F, Ivanova Alla L, Protopopova Elena V, Loktev Valery B, Osolodkin Dmitry I, Ishmukhametov Aydar A, Samygina Valeriya R
NRC «Kurchatov Institute», Moscow, Russian Federation.
FSASI "Chumakov FSC R&D IBP RAS" (Institute of Poliomyelitis), Moscow, Russian Federation.
Emerg Microbes Infect. 2024 Dec;13(1):2313849. doi: 10.1080/22221751.2024.2313849. Epub 2024 Mar 11.
Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin-Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.
蜱传脑炎病毒（TBEV）可引发一种严重疾病——蜱传脑炎（TBE），该病在欧亚大陆北部具有重大的流行病学意义。尽管有有效的甲醛灭活全病毒疫苗，但由于疫苗接种覆盖率不足以及偶发的疫苗突破病例，每年仍有10000至15000例TBE病例被登记。改进疫苗的研发将受益于抗原的原子分辨率结构。在此，我们报告了灭活的成熟TBEV疫苗株索夫金-丘马科夫（远东亚型）的单颗粒冷冻电子显微镜（cryo-EM）结构，分辨率为3.0 Å。相对于之前发表的TBEV毒株Hypr和库察洛-14（欧洲亚型）的结构，分辨率有所提高，这是由于通过优化制备方法提高了病毒样本质量。TBEV的所有表面表位在灭活病毒粒子中结构保守。用单克隆抗体进行的ELISA研究支持了甲醛灭活后TBEV蛋白衣壳交联的假说。
